Disease and damage at the level of the corneal endothelium and its basement membrane (Descemet's) may result in metaplasia of the corneal endothelial cell into fibroblast-like cell which produces a retrocorneal fibrous membrane (RCFM). This is a final common pathway for a number of corneal disease processes which result in loss of function of the corneal endothelium, corneal edema, and progressive corneal opacity and scarring. Such corneal scarring remains a leading cause of blindness in this country and the world. We have successfully studied collagen synthetic patterns in normal rabbit corneal endothelial cells and have begun to characterize these patterns in eyes with experimentally produced RCFM. Biochemical and morphologic studies have indicated an apparent change in collagen type in RCFM's. Collagen synthesis will continue to be studied in RCFM's using labeling with radioactive precursers, purification, and fractionization of collagen synthesized via SDS polyacrylamide electrophoresis and collagen typing by cyanogen bromide peptide mapping. In addition, we plan to introduce immunofluorescent techniques as a collagen typing procedure. This technique will require fewer animals with excellent specificity. The role of fibronectin as the "tissue glue" at the level of the Descemet's membrane/endothelial complex will also be studied using immunofluorescent techniques. The natural history of RCFM's biochemically and morphologically will be detailed to determine histopathogenesis of this important lesion. Fibroblastic metaplasia of corneal endothelial cells is produced experimentally by external freezing of the central cornea which results in the RCFM. Cellular elements from this material will then be studied by histopathologic and electron microscopic techniques, and collagen synthesis studied by biochemical and immunofluorescent methods. It is anticipated that delineation of the exact pathogenesis and changes occurring in these tissues will provide insight in the understanding of corneal clouding associated with disorders at the level of the corneal endothelium and Descemet's membrane, and therefore lead to possible therapy in such cases.